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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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Poly(ethylene glycol)-coated gold nanocages

, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: June 2, 2011.

Chemical name:Poly(ethylene glycol)-coated gold nanocages
Abbreviated name:PEG-AuNCs
Agent category:Metal
Target category:Non-targeted
Method of detection:Ultrasound, photoacoustic tomography (PAT) imaging
Source of signal:Gold (Au)
  • Checkbox In vitro
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No structure is currently available in PubChem.



Optical fluorescence imaging is increasingly used to monitor biological functions of specific targets (1-3). However, the intrinsic fluorescence of biomolecules poses a problem when fluorophores that absorb visible light (350–700 nm) are used. Near-infrared (NIR) fluorescence (700–1,000 nm) detection avoids the background fluorescence interference of natural biomolecules, providing a high contrast between target and background tissues. NIR fluorophores have a wider dynamic range and minimal background as a result of reduced scattering compared with visible fluorescence detection. They also have high sensitivity, resulting from low infrared background, and high extinction coefficients, which provide high quantum yields. The NIR region is also compatible with solid-state optical components, such as diode lasers and silicon detectors. NIR fluorescence imaging is becoming a noninvasive alternative to radionuclide imaging in small animals (4, 5).

Photoacoustic imaging (PAI) is an emerging hybrid biomedical imaging modality based on the photoacoustic effect. In PAI, non-ionizing optical pulses are delivered into biological tissues. Some of the delivered energy is absorbed and converted into heat, leading to transient thermoelastic expansion and thus ultrasonic emission. The generated ultrasonic waves are then detected by ultrasonic transducers to form images. It is known that optical absorption is closely associated with physiological properties, such as hemoglobin concentration and oxygen saturation. As a result, the magnitude of the ultrasonic emission (i.e., the photoacoustic signal), which is proportional to the local energy deposition, reveals physiologically specific optical absorption contrast and tissue structures. However, exogenous NIR contrast agents are necessary to overcome the intrinsic low tissue- and hemoglobin-absorption and scattering of tissue. On the other hand, these small molecules exhibit fast clearance, small optical absorption cross section, and non-targeted specificity. Therefore, there is a need for contrast agents with long blood circulation and targeted specificity.

Gold (Au) nanoparticles have been studied as molecular imaging agents because of their bright NIR fluorescence emission around 700–900 nm and low toxicity (6, 7). They can be tuned to emit in a range of wavelengths by changing their sizes, shapes, and composition, thus providing broad excitation profiles and high absorption coefficients. They can be coated and capped with hydrophilic materials for additional conjugation with biomolecules, such as peptides, antibodies, nucleic acids, and small organic compounds for in vitro and in vivo studies. Au nanoparticles have been approved by the United States Food and Drug Administration for treatment of patients with rheumatoid arthritis. Au nanoparticles have been studied as contrast agents in X-ray/computed tomography, NIR optical coherence tomography, PAI, and photoacoustic tomography (PAT) (8). NIR Au nanocages (AuNCs) are biocompatible, have low toxicity, and are tunable to strong NIR absorption (9). They have an outer edge of ~50 nm and an inner edge of ~42 nm, with a wall thickness of ~4 nm. Yang et al. (10) performed PAT of the cerebral cortex of rats with poly(ethylene glycol)-coated AuNCs (PEG-AuNCs) as the optical contrast agent. The investigators observed an enhanced optical contrast in the vasculature in the cerebral cortex.



Yang et al. (10) reported the synthesis of PEG-AuNCs by addition of 5.4 ml HAuCl4 (0.5 mM) to a 10 ml aqueous solution of Ag nanocubes containing poly(vinyl pyrrolidone) (PVP, 0.1 mg/ml) with stirring for 10 min at 100ºC. Upon cooling to room temperature, excess NaCl was added to remove Ag as AgCl. The supernatant was discarded, and AuNCs were resuspended in water. The AuNC alloy was composed of 70% Au and 30% Ag. AuNCs were washed six times to remove PVP and NaCl. AuNC surfaces were functionalized with PEG by adding 1 mL of a 1-mM PEG-SH (5 kDa) to a 2-nM AuNC suspension. The suspension was gently agitated and then allowed to sit undisturbed overnight. Residual PEG-SH was removed by centrifugation.

In Vitro Studies: Testing in Cells and Tissues


PEG-AuNCs have a maximum optical absorption at 820 nm (10). PEG-AuNCs have an outer edge of ~50 nm and an inner edge of ~42 nm, with a wall thickness of ~4 nm as estimated with scanning electron microscopy and transmission electron microscopy.

Animal Studies



Yang et al. (10) performed noninvasive PAT of one rat brain after intravenous injection of a single dose of 0.8 × 109 PEG-AuNCs/g body weight or three successive doses of 0.8 × 109 PEG-AuNCs/g. PAT scanning began immediately after injection and continued for ~3 h with the laser wavelength at 804 nm. PAT images revealed a greater optical contrast after injection with PEG-AuNCs compared with PAT imaging before injection. There was a gradual enhancement of the optical absorption in the vasculature of the cerebral cortex, with a peak value of 81% at ~2 h after the third injection. There was a gradual decrease in absorption to 40% enhancement at 6 h. In another rat with a single-dose injection, there was a peak value of 35% enhancement at ~2 h after injection.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

R01 NS46214, R01 EB000712, 5DP1 OD000798


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